The conductance mechanisms involved in the muscarinic excitation of sympathetic neurons were investigated using the single electrode voltage clamp. Type 'B' neurons in the IXth or Xth paravertebral sympathetic ganglia in bullfrog were clamped at a holding potential between -40 and -50 mV. At holding potential, the application of methylcholine (MCh) induced a slow inward current of 1-2 nA that reached peak amplitude in 1-2 min and gradually decayed over a period of 20-25 min. With voltage steps to -25 and -35 mV the outward current was usually decreased by MCh. At -70 and -90 mV, the inward current was usually increased. Removal of both Na (sucrose substitution) and Ca (Mg substitution) decreased or abolished the increased inward current induced by MCh at membrane potentials negative to -70 mV, but usually had relatively little effect on the current change induced by MCh between -35 and -70 mV. The results are consistent with at least two conductance changes in the generation of the muscarinic response. (1) a voltage-dependent decrease in K conductance at membrane potentials between -35 and -70 mV; and (2) a voltage-dependent increase in Na and/or Ca conductance at membrane potentials negative to -70 mV.